The transferable atom equivalent (TAE) modeling method is a resource-efficient alternative to routine HF/SCF ab initio calculations, Electron density representations created by TAE reconstruction are designed to allow numerous molecular properties to be quickly assessed with results similar to those obtained at the HF/6-31 + G(*) level of theory. While Hartree-Fock calculations using this basis set do not provide state-of-the-art results in many areas, they do give a good representation of molecular geometries and of most ground-state electronic properties. In contrast to traditional ab initio methods, the CPU and disk resources required for TAE reconstruction are comparable to those utilized by molecular mechanics geometry optimizations. TAE modeling involves retrieval of a set of appropriate atomic electron density representations from the TAE library, followed by a self-consistent assembly process in which each atom adjusts slightly to its new environment. Atomic electronic properties are affected by this adjustment, and can be queried separately to give atom-centered results or combined to yield molecular properties. An automated version of our RECON assembly program is under development which can be used to rapidly scan large databases for specific combinations of molecular electron density properties such as the spatial distributions of electrostatic potential fields or other electron density properties. The TAE library currently contains 64 atom types which were derived by 18-dimensional cluster analysis of the electron density properties of over 6000 integrated atoms. Good agreement with ab initio results is observed when the molecules under investigation are small enough to permit direct comparison with HF/6-31 + G(*) Gaussian92 calculations. TAE reconstructions of very large molecular systems cannot be calibrated by direct comparison with ab initio results, so validation of the method is done using piece wise comparison with smaller model compounds. A brief analysis of the binding of the immunosuppressant drug FK506 with FKBP is presented as an example of large-molecule/small-molecule interaction modeling using the TAE method.
